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在第二代α1-酸性糖蛋白手性固定相上直接高效液相色谱法测定血浆中阿夫唑嗪对映体

Direct high-performance liquid chromatographic determination of the enantiomers of alfuzosin in plasma on a second-generation alpha 1-acid glycoprotein chiral stationary phase.

作者信息

Rouchouse A, Manoha M, Durand A, Thenot J P

机构信息

Synthélabo Recherche, L.E.R.S., Paris, France.

出版信息

J Chromatogr. 1990 May 11;506:601-10. doi: 10.1016/s0021-9673(01)91608-5.

DOI:10.1016/s0021-9673(01)91608-5
PMID:2376608
Abstract

A direct liquid chromatographic method was developed for the determination of the enantiomers of alfuzosin in human plasma, without derivatization, on a chiral alpha 1-acid glycoprotein column. The influence of pH, of uncharged organic solvents and of a cationic modifier (tetrabutylammonium) of the mobile phase on retention and enantioselectivity was evaluated. The enantiomers and an internal standard, structurally related to alfuzosin, were extracted from plasma with dichloromethane-diethyl ether from alkaline solution, then separated with a mobile phase of 0.025 M phosphate buffer (pH 7.4) containing 0.025 M tetrabutylammonium bromide-acetonitrile (94:6, v/v). The limit of quantification for each isomer was 1 ng/ml. The method has been applied to the determination of the pharmacokinetic profile of alfuzosin enantiomers in healthy volunteers after intravenous administration of the racemate.

摘要

建立了一种直接液相色谱法,用于在未衍生化的情况下,在手性α1-酸性糖蛋白柱上测定人血浆中阿夫唑嗪对映体。评估了流动相的pH值、中性有机溶剂和阳离子改性剂(四丁基铵)对保留和对映体选择性的影响。对映体和与阿夫唑嗪结构相关的内标物,用二氯甲烷-乙醚从碱性溶液中萃取血浆,然后用含0.025 M溴化四丁基铵-乙腈(94:6,v/v)的0.025 M磷酸盐缓冲液(pH 7.4)作为流动相进行分离。每种异构体的定量限为1 ng/ml。该方法已应用于在健康志愿者静脉注射消旋体后测定阿夫唑嗪对映体的药代动力学特征。

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